Mechanisms for acute stress-induced enhancement of glutamatergic transmission and working memory

Mol Psychiatry. 2011 Feb;16(2):156-70. doi: 10.1038/mp.2010.50. Epub 2010 May 11.

Abstract

Corticosteroid stress hormones have a strong impact on the function of prefrontal cortex (PFC), a central region controlling cognition and emotion, though the underlying mechanisms are elusive. We found that behavioral stressor or short-term corticosterone treatment in vitro induces a delayed and sustained potentiation of the synaptic response and surface expression of N-methyl-D-aspartic acid receptors (NMDARs) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) in PFC pyramidal neurons through a mechanism depending on the induction of serum- and glucocorticoid-inducible kinase (SGK) and the activation of Rab4, which mediates receptor recycling between early endosomes and the plasma membrane. Working memory, a key function relying on glutamatergic transmission in PFC, is enhanced in acutely stressed animals through an SGK-dependent mechanism. These results suggest that acute stress, by activating glucocorticoid receptors, increases the trafficking and function of NMDARs and AMPARs through SGK/Rab4 signaling, which leads to the potentiated synaptic transmission, thereby facilitating cognitive processes mediated by the PFC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Biophysics
  • Cells, Cultured
  • Corticosterone / pharmacology
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Electric Stimulation
  • Excitatory Amino Acid Agents / pharmacology
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / genetics
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / genetics
  • Glutamic Acid / metabolism*
  • Green Fluorescent Proteins / genetics
  • Hormone Antagonists / pharmacology
  • Immediate-Early Proteins / genetics
  • Immediate-Early Proteins / metabolism
  • In Vitro Techniques
  • Long-Term Potentiation / drug effects
  • Male
  • Maze Learning / drug effects
  • Maze Learning / physiology
  • Memory, Short-Term / drug effects*
  • Memory, Short-Term / physiology*
  • Mifepristone / pharmacology
  • Patch-Clamp Techniques / methods
  • Peptides / pharmacology
  • Prefrontal Cortex / cytology
  • Prefrontal Cortex / drug effects*
  • Prefrontal Cortex / physiopathology*
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism
  • Pyramidal Cells / drug effects
  • Pyramidal Cells / physiology
  • RNA, Small Interfering / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Glutamate / genetics
  • Receptors, Glutamate / metabolism
  • Stress, Psychological / pathology
  • Stress, Psychological / physiopathology
  • Synaptic Transmission / drug effects*
  • Time Factors
  • Transfection / methods
  • rab GTP-Binding Proteins / genetics
  • rab GTP-Binding Proteins / metabolism

Substances

  • Excitatory Amino Acid Agents
  • Hormone Antagonists
  • Immediate-Early Proteins
  • Peptides
  • RNA, Small Interfering
  • Receptors, Glutamate
  • Green Fluorescent Proteins
  • Mifepristone
  • Glutamic Acid
  • Protein-Serine-Threonine Kinases
  • serum-glucocorticoid regulated kinase
  • rab GTP-Binding Proteins
  • Corticosterone